3,113 research outputs found
Emerging priorities for HIV service delivery
Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services
A reaction-diffusion model of cholinergic retinal waves
Prior to receiving visual stimuli, spontaneous, correlated activity called
retinal waves drives activity-dependent developmental programs. Early-stage
waves mediated by acetylcholine (ACh) manifest as slow, spreading bursts of
action potentials. They are believed to be initiated by the spontaneous firing
of Starburst Amacrine Cells (SACs), whose dense, recurrent connectivity then
propagates this activity laterally. Their extended inter-wave intervals and
shifting wave boundaries are the result of the slow after-hyperpolarization of
the SACs creating an evolving mosaic of recruitable and refractory cells, which
can and cannot participate in waves, respectively. Recent evidence suggests
that cholinergic waves may be modulated by the extracellular concentration of
ACh. Here, we construct a simplified, biophysically consistent,
reaction-diffusion model of cholinergic retinal waves capable of recapitulating
wave dynamics observed in mice retina recordings. The dense, recurrent
connectivity of SACs is modeled through local, excitatory coupling occurring
via the volume release and diffusion of ACh. In contrast with previous,
simulation-based models, we are able to use non-linear wave theory to connect
wave features to underlying physiological parameters, making the model useful
in determining appropriate pharmacological manipulations to experimentally
produce waves of a prescribed spatiotemporal character. The model is used to
determine how ACh mediated connectivity may modulate wave activity, and how the
noise rate and sAHP refractory period contributes to critical wave size
variability.Comment: 38 pages, 10 figure
Providing antiretroviral care in conflict settings.
There has been an historic expectation that delivering combination antiretroviral therapy (cART) to populations affected by violent conflict is untenable due to population movement and separation of drug supplies. There is now emerging evidence that cART provision can be successful in these populations. Using examples from Médecins Sans Frontières experience in a variety of African settings and also local nongovernmental organizations' experiences in northern Uganda, we examine novel approaches that have ensured retention in programs and adequate adherence. Emerging guidelines from United Nations bodies now support the expansion of cART in settings of conflict
Mortality after fluid bolus in children with shock due to sepsis or severe infection: a systematic review and meta-analysis.
Sepsis is one of the leading causes of childhood mortality, yet controversy surrounds the current treatment approach. We conducted a systematic review to assess the evidence base for fluid resuscitation in the treatment of children with shock due to sepsis or severe infection
How developing world concerns need to be part of drug development plans: A case study of four emerging antiretrovirals
Clinical trials are usually designed to meet registration requirements in developed countries, and do not always address key concerns for use in developing countries. Four late-stage investigational new drugs - rilpivirine, etravirine, raltegravir and maraviroc - show potential to improve antiretroviral therapy. However, a number of issues could limit their use in developing countries, including dose selection, treatment strategy, combination with other drugs, use in specific populations and reliance on expensive tests. Key research questions relevant for developing countries need to be answered early in the drug development process to ensure maximum benefit for the majority
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